Deparment of Medical Genetics, Dr. Zekai Tahir Burak Women Health Training and Research Hospital, Ankara-Turkey.
Environ Toxicol. 2011 Aug;26(4):395-402. doi: 10.1002/tox.20691. Epub 2011 Mar 7.
Acute renal failure resulting from radiocontrast-induced nephrotoxicity (RIN) is suggested to occur via medullary ischemia coupled with the generation of free radicals and oxidative injury to tubular cells. The aim of the present study was to assess the effects of erdosteine on prevention of RIN. Thirty-three Wistar-albino rats were divided into five groups: control (group 1, n = 6), radiocontrast media (group 2, n = 6), erdosteine (group 3, n = 7), erdosteine four doses before radiocontrast application (group 4, n = 7) and erdosteine one dose at the same day with radiocontrast application (group 5, n = 7). RIN was induced by administration of intravenous high osmolar contrast media amidotrizoate (6 mL/kg). Total RNA was extracted from the kidney, and the expression levels of Lipocalin 2 (Lcn2) and secreted phosphoprotein 1 (Spp1) genes were evaluated by real time reverse transcription polymerase chain reaction (real-time RT-PCR). Total antioxidant status (TAS) and total oxidant status (TOS) were measured in kidney homogenates and serum samples. Serum creatinine, BUN (Blood Urea Nitrogen) and cystatin-C levels were measured from serum samples. The kidneys were evaluated histopathologically. The expression levels of Spp1 and Lcn2 genes in group 2 were significantly higher than groups 1, 3, 4, and 5. The expression levels of Spp1 and Lcn2 genes in group 4 were four and two times lower than group 5, respectively. Kidney TOS levels in group 2 were significantly higher than groups 1, 3, 4, and 5. Kidney TAS levels in group 3 were higher than group 2. Kidney oxidative stress index (OSI) levels in group 2 were significantly higher than groups 4 and 5. All rats in contrast media group developed tubular necrosis, proteinaceous casts, medullary congestion although these changes were significantly reduced in groups 4 and 5. This study demonstrated that multiple doses of erdosteine before application may have higher protective effects against RIN.
急性肾衰由放射造影剂诱导的肾毒性(RIN)引起,据推测是通过髓质缺血以及自由基的产生和肾小管细胞的氧化损伤引起的。本研究旨在评估厄多司坦对预防 RIN 的作用。33 只 Wistar 白化大鼠分为五组:对照组(第 1 组,n = 6)、放射造影剂组(第 2 组,n = 6)、厄多司坦组(第 3 组,n = 7)、厄多司坦在放射造影剂应用前 4 个剂量组(第 4 组,n = 7)和厄多司坦在同一天与放射造影剂应用 1 个剂量组(第 5 组,n = 7)。通过静脉注射高渗造影剂 amidotrizoate(6 mL/kg)诱导 RIN。从肾脏提取总 RNA,并通过实时逆转录聚合酶链反应(实时 RT-PCR)评估脂质运载蛋白 2(Lcn2)和分泌型磷蛋白 1(Spp1)基因的表达水平。在肾匀浆和血清样本中测量总抗氧化状态(TAS)和总氧化状态(TOS)。从血清样本中测量血清肌酐、BUN(血尿素氮)和胱抑素 C 水平。对肾脏进行组织病理学评估。第 2 组的 Spp1 和 Lcn2 基因表达水平明显高于第 1、3、4 和 5 组。第 4 组的 Spp1 和 Lcn2 基因表达水平分别比第 5 组低 4 倍和 2 倍。第 2 组的肾脏 TOS 水平明显高于第 1、3、4 和 5 组。第 3 组的肾脏 TAS 水平高于第 2 组。第 2 组的肾脏氧化应激指数(OSI)水平明显高于第 4 组和第 5 组。所有接受造影剂的大鼠均发生肾小管坏死、蛋白样铸型、髓质充血,尽管这些变化在第 4 组和第 5 组中明显减轻。本研究表明,应用前多次给予厄多司坦可能对 RIN 具有更高的保护作用。